title: Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor.
abstract: Herpes simplex virus entry into cells requires the binding of envelope glycoprotein D (gD) to an entry receptor. Depending on the cell, entry occurs by different mechanisms, including fusion at the cell surface or endocytosis. Here we examined the entry mechanism through a non-HSV receptor mediated by a soluble bi-specific adapter protein composed of recognition elements for gD and the EGF receptor (EGFR). Virus entered into endosomes using either EGF or an EGFR-specific single chain antibody (scFv) for receptor recognition. Infection was less efficient with the EGF adapter which could be attributed to its weaker binding to a viral gD. Infection mediated by the scFv adapter was pH sensitive, indicating that gD-EGFR bridging alone was insufficient for capsid release from endosomes. We also show that the scFv adapter enhanced infection of EGFR-expressing tumor tissue in vivo. Our results indicate that adapters may retarget HSV infection without drastically changing the entry mechanism.
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan. kenakano@med.kyushu-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kei-ichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Asano
authors.forename: Izumi
authors.initials: I
authors.lastname: Kumagai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tahara
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
authors.forename: Justus B
authors.initials: JB
authors.lastname: Cohen
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D057127:Single-Chain Antibodies; D014759:Viral Envelope Proteins; D066246:ErbB Receptors